A Study to Evaluate and Characterize the Effect of Pharmacological Chemicals on Blood From Patients With Gaucher Disease

Completed

Conditions studied: Gaucher Disease

In brief

Gaucher disease is a lysosomal storage disorder resulting from a deficiency in the key enzyme b-glucocerebrosidase (GCase). This enzyme is responsible for breaking down a specialized type of fat molecule, known as glucocerebroside, in the lysosome. The enzyme deficiency is caused by genetic mutations which result in the production of misfolded GCase protein. The absent or defective GCase enzyme activity leads to build-up of glucocerebroside inside certain cells. Over time, these Gaucher cells can accumulate and may cause inflammation or damage to specific areas within the body, including the liver, spleen, bone marrow, lung, and the central nervous system. AT2101 is designed to act as a pharmacological chaperone by selectively binding to the misfolded GCase. After binding to the enzyme, it is thought that AT2101 promotes the proper folding, processing, and trafficking of the enzyme from the endoplasmic reticulum to its final destination, the lysosome, the area of the cell where the enzyme does its work. Once it reaches the lysosome, the pharmacological chaperone is displaced and the enzyme can perform its normal function, which is the breakdown of its natural substrate, glucocerebroside. Several in vitro and in vivo preclinical studies have been conducted. In these studies AT2101 increased GCase enzyme level in cells derived from Gaucher disease patients with different genetic mutations, including cells with a genetic mutation associated with the neurologic form of Gaucher disease. In normal mice, oral administration of AT2101 resulted in a dose-dependent increase in GCase level in the liver, spleen, brain, and lung. This study is designed to evaluate the ex vivo response to pharmacological chaperone therapy by testing blood samples from previously treated and untreated patients with Gaucher disease. The study will include patients with non-neuropathic Gaucher disease (type I) and neuropathic Gaucher disease (types II and/or III). Up to 50 patients will be enrolled at the NIH. All subjects will participate in one study visit. Clinical information will be collected retrospectively from medical records. Information collected will include Gaucher disease diagnosis and history, medical history, family history, assessments of clinical severity, and genotype. A blood sample will be collected and various cells will be isolated for laboratory testing and research.

Key facts

Study ID

NCT00465062

Run by

National Institute of Neurological Disorders and Stroke (NINDS)

People needed

50

Starts

2007-04-19

Expected to finish

2008-03-03

Last updated by the study team

2017-07-02

Who can join

Age: any. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

• To be eligible for the study, subjects must not fulfill any of the following exclusion criteria:
• Received any investigational product within 30 days prior to study entry.
• Other significant disease or be otherwise unsuitable for the study, as determined by the investigator.

Where it is running

• National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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